Summary: Infections due to Neisseria gonorrhoeae represent a significant cause of morbidity and mortality in women and children throughout the world. The pathogenesis of gonococcal infections is not well understood, particularly with respect to the effect of patient hormonal status on the infectious disease process. Currently, there are no licensed vaccines for prevention of gonorrhea. This project will investigate the effect of reproductive hormones, estradiol and progesterone, and oral contraceptives, on the expression of gonococcal outer membrane antigens in both the laboratory and clinical settings. We will also evaluate whether or not these hormones affect attachment and/or invasion to human cervical and endometrial tissue culture cells. The goal is identify potential new antigens that may be particularly relevant in gonococcal infections in women and to determine if hormonal status may be a factor to be considered in the evaluation of models of infection. Purpose and Objectives The purpose of this project is to evaluate the effect of female reproductive and contraceptive hormones on the pathogenesis of N. gonorrhoeae. Our objective is to identify gonococcal surface antigens that may be subject to hormonal regulation. A second objective is to evaluate hormonal effects on gonococcal adherence and invasion to cells grown in tissue culture. Because there are no animal models of gonococcal infection, tissue culture cells are routinely used to evaluate the ability of antibodies to vaccine candidates to inhibit adherence and/or invasion. Initial studies to evaluate expression of these antigens during human infection will be conducted on clinical isolates from a STD clinic population. The specific aims of this project are: 1. to assess the effect of estradiol and progesterone on expression of gonococcal outer membrane antigens; and 2. to determine whether estradiol and progesterone alter gonocooccal adherence and/or invasion to human cells.